A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.

Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors / Pau, Amedeo; Asproni, Battistina; Murineddu, Gabriele; Boatto, Gianpiero; Grella, Giuseppe Enrico; Rakowitz, D.; Costantino, L.; Pinna, Gerard Aime. - In: MEDICINAL CHEMISTRY. - ISSN 1573-4064. - 2:1(2006), pp. 39-45. [10.2174/157340606775197769]

Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors

PAU, Amedeo;ASPRONI, Battistina;MURINEDDU, Gabriele;BOATTO, Gianpiero;GRELLA, Giuseppe Enrico;PINNA, Gerard Aime
2006-01-01

Abstract

A new series of 8-halogen-4,4a,5,6-tetrahydrothieno[2,3-h]cinnolinone-N2-alkanoic acids was prepared and tested for aldose reductase (ALR2) inhibitory activities. These compounds showed significant inhibitory activity against bovine lens ALR2, with the best compound 2e showing an IC(50) value of 31.4 microM. The presence of the C8-substituents here studied (Cl, Br) on the thienocinnolinone scaffold caused a decrease of the inhibitory potency by a factor of about 4 with respect to the unsubstituted parent compound, while the presence of a C8-methyl group, considered in a previous paper decreased the activity by a factor of about 2. Moreover, the length of the N2 alkanoic chain influences strongly the enzyme inhibitory activity. While most of the carboxylic acids ALR2 inhibitors are acetic acid derivatives, in the case of thienocinnolinone compounds, homologues higher than acetic acids showed to be more active.
2006
Thienocinnolinone alkanoic acid derivatives as aldose reductase inhibitors / Pau, Amedeo; Asproni, Battistina; Murineddu, Gabriele; Boatto, Gianpiero; Grella, Giuseppe Enrico; Rakowitz, D.; Costantino, L.; Pinna, Gerard Aime. - In: MEDICINAL CHEMISTRY. - ISSN 1573-4064. - 2:1(2006), pp. 39-45. [10.2174/157340606775197769]
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/45654
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? ND
social impact